The polymorphic fungus Candida albicans is a commensal organism that colonizes the gastrointestinal tract, vagina and some cutaneous areas of the majority of healthy humans. However, under certain conditions the fungus is able to cause a variety of infections, ranging from mucosal to life-threatening invasive candidiasis (18). C. albicans continues to be the most common cause of various forms of candidaisis (34, 47), but several other Candida spp. are also important agents. Invasive disease is associated with billions of dollars each year in healthcare costs and a mortality rate estimated at ˜40% (32, 33). The limited number and toxicity of antifungal agents, and, most importantly, the poor outcome of almost half of the number of candidemia patients treated with appropriate antifungal therapy, militates in favor of disease prevention, possibly through active and passive immunization strategies (10, 15, 41).
The protective role of antibodies against Candida has been controversial, but the evidence is mounting in favor for this mode of protection. Specificity of protective antibodies may be for C. albicans cell wall polysaccharides, proteins and peptides (13, 17, 40, 53, 55). As a prevention strategy, protection against disease may be actively or passively acquired by vaccination and transfer of preformed monoclonal antibodies, respectively. As a therapeutic measure, experimental evidence indicates that preformed antibodies may enhance the effectiveness of antifungal agents (24, 43).
The first fully synthetic glycopeptide vaccines against C. albicans induced protection against disseminated candidiasis in mice (53). Six putative T-cell peptides found in C. albicans cell wall proteins were conjugated to the protective β-1,2-mannotriose [β-(Man)3] glycan epitope to create glycopeptide conjugates. The six proteins from which the peptides, denoted in parentheses, were derived because of expression during human candidiasis and cell wall association and included: fructose-bisphosphate aldolase (Fba) (YGKDVKDLDYAQE; SEQ ID NO:1); methyltetrahydropteroyltriglutamate homocysteine methyltransferase (Met6) (PRIGGQRELKKITE; SEQ ID NO:2); hyphal wall protein-1 (Hwp1) (QGETEEALIQKRSY; SEQ ID NO:3); enolase (Enol) (DSRGNPTVEVDFTT; SEQ ID NO:4); glyceraldehyde-3-phosphate dehydrogenase (Gap1) (NRSPSTGEQKSSGI; SEQ ID NO:5); and phosphoglycerate kinase (Pgk1) (VPLDGKTITNNQRI; SEQ ID NO:6) (53). The intent of this work was that the peptides would serve as T-cell epitopes, promoting protective antibody responses against the glycan part of the glycopeptide conjugates. Thus, the immunization protocols were designed to favor antibody, rather than cell-mediated immune (CMI) responses and antibodies were generated against both the glycan and peptide parts of the various conjugates. That is, by DC based immunization protocols favoring antibody production, the three glycoconjugates β-(Man)3-Fba, β-(Man)3-Meth and β-(Man)3-Hwp1 induced protection from hematogenous challenge with the fungus as evidenced by mouse survival and low kidney fungal burden (53). The β-(Man)3-Enol and β-(Man)3-Gap1 gave moderate protection, and the β-(Man)3-Pgk1 slightly enhanced disease. For the β-(Man)3-Fba conjugate, protection was uniquely acquired through immunity against the glycan and the Fba peptide. The native protein fructose-1,6-bisphosphate aldolase (Fba1p), which catalyzes the reversible cleavage of fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, has become an attractive antifungal target for several reasons. First, this key enzyme is required for growth on both fermentative and nonfermentative carbon sources; therefore it is essential for C. albicans viability and other pathogenic fungi (48). Second, fungal fructose-1,6-bisphosphate aldolases are distinct from human fructose-1,6-bisphosphate aldolases. C. albicans Fba1p belongs to the family of class II aldolases found predominantly in fungi and prokaryotes (39). In contrast, the human enzyme belongs to the class I aldolases, and the sequence of human aldolase is significantly different from those of fungal aldolases (39), thus it is reasonable to expect that it may be possible to achieve an immunologic response specific only to the fungal enzyme. Indeed, the Fba 14 mer peptide sequence (YGKDVKDLFDYAQE; SEQ ID NO:1) is unique to C. albicans (53).
U.S. Pat. No. 4,771,127 discloses polysaccharide-protein conjugate vaccines synthesized using polysaccharide derived from Pseudomonas aeruginosa lipopolysaccharide coupled to either tetanus toxoid or P. aeruginosa toxin A.
U.S. Pat. Nos. 5,578,309; 6,488,929; and 6,30,146 disclose vaccines for Candida albicans based on the isolated phosphomannoprotein cell wall complexes of C. albicans, including β-1,2-linked tri-mannose residues.
U.S. Pat. Nos. 6,309,642; 6,391,587; and 6,403,090 and U.S. Patent Application Publication U.S. 2003/0072775 disclose vaccines based on peptides that mimic phosphormanna epitopes or polyneucleotides encoding the peptide mimotopes, and discloses monoclonal antibodies, including MAb B6.1, for passive immunization against infections of Candida albicans. 
U.S. Pat. No. 7,722,890; U.S. Patent Application Publication Nos. 2006/0058506, 2008/0193481 and 2010/0209448; and International Publication Nos. WO 03/090787 and WO 2006/096970 disclose vaccines against Candida species based on immunogenic oligosaccharide compositions comprising native O-linked and S-linked oligosaccharides, including β-(1-2)-β-D-mannopyrose triose (also referred to as β-(Man)3 or β-(1,2)-mannotriose), coupled to a protein carrier, including the protein carrier tetanus toxoid.